P920: EVALUATION OF EARLY PROGRESSIVE DISEASE (EPD) IN NEWLY DIAGNOSED MYELOMA PATIENTS AND IDENTIFICATION OF PROGNOSTIC FACTORS IN THE ERA OF MODERN THERAPIES. THE GREEK MYELOMA STUDY GROUP EXPERIENCE.
Authors: Eirini Katodritou, Efstathios Kastritis, Dimitra Dalampira, Fotini Theodorakakou, Despina Fotiou, Sosana Delimpasi, Emmanouil Spanoudakis, Ioannis Ntanasis-Stathopoulos, Theodosia Papadopoulou, Aggeliki Sevastoudi, Theodora Triantafyllou, Aikaterini Daiou, Anastasia Pouli, Magdalini Migkou, Maria Gavriatopoulou, Evgenia Verrou, Marie Christine Kyrtsonis, Meletios A. Dimopoulos, Evangelos Terpos
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Despite treatment improvements there is still a respectable proportion of newly diagnosed multiple myeloma (MM) patients that experience early progressive disease (EPD) defined as relapse or progression <18 months from start of therapy. Aims: Herein we describe the clinical characteristics and outcomes of patients with EPD and examine the prognostic ability of staging systems, molecular cytogenetics, and type of upfront treatments to determine the risk for EPD, in the current therapeutic landscape. Methods: We evaluated 1436 newly diagnosed MM (M/F: 700/736; median age: 67, range 29-90; IgG: 841, IgA: 395, light chain: 162, IgD: 11, non-secretory: 24, IgM: 3) with complete data for international staging system (ISS) and R-ISS. All patients included in the analysis had achieved at least MR to primary therapy and had complete data regarding 1st line treatment and outcomes. Comparisons of patients’ characteristics was performed with Mann-Whitney-U test, One-Way-ANOVA and X2. A binary logistic regression analysis was performed to determine significant prognostic factors for EPD; p<0.05 was considered as statistically significant. Results: Early progressive disease was observed in 335/1436 (23.3%). Patients with EPD had higher median age (68 vs. 66; p<0.001), β2-microglobulin, LDH and bone marrow infiltration and lower hemoglobin and eGFR, compared to non-EPD (p<0.05); ISS-3 and R-ISS3 were more frequent in patients with EPD (34% vs. 26%; p<0.001 and 19% vs. 10%; p<0.001, respectively). Data for second revision of ISS (R2-ISS) was available in 73% of patients: R2-ISS III and IV were more frequent in patients with EPD (63% vs. 42%; p<0.001). Presence of ≥2 high-risk molecular abnormalities i.e. del17p, t(4;14), t(14;16) or +1q21 (ultra-high risk myeloma) was also more frequent in the EPD group (13.5% vs. 6.6%; p<0.001). The percentage of patients treated with lenalidomide-based therapies (LBT), including triplets, did not differ between groups (EPD: 29% vs. others: 33%; p>0.05), whereas daratumumab-based therapies (DBT) were administered less frequent in patients with EPD vs. others (2% vs. 10%; p<0.001). Autologous stem cell transplantation (ASCT) was given in 11% of patients with EPD vs. 33% of non-EPD (p<0.001). Binary logistic regression analysis demonstrated that ISS, R-ISS, R2-ISS, ultra-high-risk myeloma, ASCT and DBT were significant predictors for EPD (p<0.05); LBT did not have any prognostic value in the univariate analysis (p>0.05). In the multivariate analysis R2-ISS, ASCT and DBT were the stronger significant prognosticators for EPD (HR for R2-ISS: (I) vs. (IV): 0.24; p<0.001, (II) vs. (IV): 0.28; p<0.001, (III) vs. (IV): 0.48; p=0.017), HR for ASCT: 0.26; p<0.001, and HR for DBT: 0.18; p<0.001). After a median follow up of 77 months (95% CI: 72-83), median progression free survival and overall survival for patients with EPD vs. others were 10 vs. 40 months (p<0.001) and 29 vs.76 months (p<0.001), respectively. Summary/Conclusion: In conclusion, we have showed that, >20% of newly diagnosed MM patients experienced EPD, in the real-world setting; EPD patients were more frequently older, with higher tumor burden and high-risk features. Upfront DBT and ASCT were the strongest prognostic factors, reducing by 82% and 74%, respectively the risk for EPD; R2-ISS proved a significant predictor for EPD however, its value was mitigated when adjusted to the type of primary therapies. These findings suggest that patients with EPD represent an unmet clinical need and deserve dedicated prospective trials to evaluate novel treatment approaches. Keywords: Multiple myeloma, Progression